The effect of leukotrienes C 4 and D 4 on the microvasculature of guinea-pig skin

Abstract

The effects of chemically-synthesised leukotrienes C 4 and D 4 (5(S) hydroxy-6(R)-δ-glutamylcysteinylglycinyl-7,9,11,14-eicosa- 4tetraenoic acid, LTC 4; 5(S) hydroxy-6(R)-cysteinylglycinyl-7,9,11,14-eicosatetraenoic acid, LTD 4) on the microvasculature have been measured in guinea-pig skin using [ 125I]-albumin accumulation to measure plasma exudation and 133Xe clearance to measure blood flow changes. As previously shown using biosynthetic material, LTD 4 caused vasoconstriction resulting in reduced blood flow. Similarly, LTC 4 was found to have vasoconstrictor activity but was more potent and had a steeper dose-response curve than LTD 4. There was no evidence of conversion of exogenous arachidonic acid to vaso-constrictor activity in the skin in vivo (in the absence of another stimulus): intradermally injected arachidonic acid produced vasodilatation, but induced little change in blood flow in animals pretreated with indomethacin. The vasodilator effect of arachidonic acid is presumed to be due to conversion to either PGE 2 or PGI 2. These results suggest that cyclo-oxygenase is normally active in the skin, whilst lipoxygenase requires activation in some way. As reported in a previous study, LTD 4 induced plasma exudation when injected into the skin, but pronounced responses could only be induced by LTD 4 mixed with a vasodilator prostaglandin such as PGE 2. In contrast, LTC 4 induced no exudation when tested alone and little when PGE 2 was added. However, evidence was obtained that LTC 4 has some permeability-increasing activity which is marked by its potent vasoconstrictor activity.